The goal of this project is to understand how neural signals are transmitted in the retina, from photoreceptors through bipolar neurons to the ganglion cells. Because of the central position of bipolar neurons in this signal path, the synaptic contacts made by bipolar neurons are a vital link in the transmission and processing of visual information. Therefore, one major focus of this project is the mechanism of neurotransmitter release from synaptic terminals of retinal bipolar neurons. Chemical neurotransmitter is released from synaptic terminals via exocytosis of synaptic vesicles, and the membrane of fused vesicles is then retrieved by endocytosis. These fundamental processes of synaptic exocytosis and endocytosis will be examined in multidisciplinary experiments combining optical, electrophysiological, molecular, and anatomical approaches. Because neurotransmitter release is controlled by presynaptic calcium influx, experiments will also be conducted to determine the mechanisms controlling internal calcium in synaptic terminals, including the calcium channels that support calcium entry and the extrusion and buffering mechanisms that regulate intracellular calcium concentration. Ultimately, the visual signal leaving the retina is encoded in action potentials in the ganglion cell axons of the optic nerve. The second major focus of the project is the channels that generate action potentials, voltage-dependent sodium channels. Knowledge of the physiological and molecular properties of these channels is required to understand the encoding and transmission of visual information. Multiple sodium-channel genes are expressed in the retina, and experiments will be conducted to examine the differential targeting of sodium channel isoforms in retinal neurons. The functional implications of the localization of particular sodium channel isoforms to specific regions of ganglion cell axons will also be investigated. The roles of voltage-gated sodium channels in the dendritic propagation of synaptic signals will also be studied in cells that do not produce action potentials, such as retinal bipolar neurons. These two lines of research will provide information about basic aspects of retinal signal processing. The results will also be of general significance for neuronal function in other parts of the nervous system outside the retina.